Transcript Managing atrophic vaginitis after breast cancer

Managing Menopausal Symptoms
after Breast Cancer
Rod Baber
What are menopausal symptoms ?
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Vasomotor symptoms:
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hot flushes
night sweats
Vulvo-vaginal dryness
Sleep disturbance
Mood disturbance
Sexual dysfunction
NIH State-of-the-Science Panel. Ann Intern Med 2005
Why do breast cancer patients get
menopausal symptoms?
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Around 60% affected
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Young women with chemotherapy-induced ovarian failure
Young women undergoing oophorectomy
Peri and postmenopausal women who stop HRT on
diagnosis of breast cancer
Pre and postmenopausal women taking endocrine therapy
(for up to 10 years)
Hot flushes are more frequent and severe than in
spontaneous menopause
Anti-estrogen therapies may exacerbate symptoms:
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Vaginal dryness particularly severe with aromatase inhibitors
Hickey et al 2008, Kemp et al 2014, Marino et al 2014, Howell et al 2005, ACOG 2014
Why are menopausal symptoms after
breast cancer problematic?
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They may impair quality of life:
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May impact on tolerance of endocrine therapy
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Worse than the cancer treatment for some women
Up to 40% discontinue because of hot flushes
May add to common post-cancer problems such as
sleep disturbance and fatigue
May have implications for prognosis
Risks of early menopause may contribute to morbidity
and mortality
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Osteoporosis and cardiovascular disease
Howard-Anderson et al 2012, Chen et al 2013
How long do hot flushes last ?
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Most severe symptoms
around the LMP
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Mean
duration
of
vasomotor symptoms at
natural menopause is 8-10
years
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Duration after surgical or
chemo-induced menopause
unknown
Politi et al 2008, Col et al 2008, Freeman et al 2014
How can symptoms be managed?
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Most women have several symptoms
Vasomotor symptom are the most
common reason to seek treatment, but
additive effect of symptoms is unknown
Estrogen is the most effective treatment
for VMS (85% reduction) and also
improves
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Vulvo-vaginal dryness
Potentially mood and sleep
Bone health
MacLennan et al 2006, Suckling et al 2006, Soares and Frey 2010, Formoso et al 2012
Menopausal symptoms after breast
cancer: what can be done?
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No single non-hormonal treatment for VMS,
vaginal symptoms, mood and bone health
Need to prioritise and consider multiple
interventions
Effective non-pharmacological and non-hormonal
therapies are available
Tailor interventions to individual symptom burden
Managing Menopausal
Symptoms after Breast Cancer
1. Assess Cause of menopausal symptoms
Discontinued
HRT
Endocrine
Treatment induced
Therapy
menopause
2. Assess menopausal symptoms
Hot flushes, night sweats, insomnia
Joint aches and pains, vaginal dryness….
3. Establish what is wanted from Intervention
Reduction in (what) symptoms
Information / Other outcomes
Managing atrophic vaginitis after
breast cancer
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Prevalence after breast cancer unknown
Affects ~ 40% at menopause
 Vaginal dryness, discomfort, pruritis, dyspareunia, UTI, urgency
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Worse with AI than tamoxifen
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Vaginal Lubricants:
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Vaginal Moisturisers: Replens
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Vulval Lignocaine gel 4%
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Vaginal Estrogens -Ovestin (Oestriol), Vagifem (E2) tablets
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Ospemifene
Sylk, Astroglide, Passion, Wet, Olive oil
Suckling et al 2006, Dorr et al 2010, Maarmari 2013, Barentsen et al 1997, Burich et al 2012
Managing atrophic vaginitis after
breast cancer
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Vaginal estrogens are the most effective
treatment, but are systemically absorbed
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Vaginal estradiol significantly increases systemic E2 in
users of aromatase inhibitors
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Many oncologists now caution against their use
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Clinical implications unknown
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Tamoxifen is probably estrogenic in vagina
Kendall et al 2006, Ferrazzi et al 1977, Freidrich et al 1998
Managing atrophic vaginitis
after breast cancer
Clinical message
 Avoid
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vaginal estrogens in AI users
considering then discuss with oncologist
 Consider
 Still
vaginal estrogens in TAM users
discuss with oncologist
 Relative
efficacy of vaginal lubricants unknown
 Vulval
lignocaine (4%) reduces dyspareunia and
sexual distress in breast cancer survivors
Goetsch et al 2014
Treating VMS without hormones
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Target day or night VMS
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Review the likely “cause” of the VMS
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Getting a good nights sleep may make the day manageable
Early menopause
Stopping HRT
Endocrine therapy
Interventions may differ depending on cause
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Some VMS improve by swapping endocrine therapies
Thomas et al 2008. Hickey et al 2008, Baum et al 2008
Alternative Therapies
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Phytoestrogens:
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Pure isoflavones may be effective, but mixed evidence to
suggest that supplements are effective.
Genistein reduces hot flush frequency (20%) and severity
(26%) compared to placebo
Black Cohosh: Data mixed but insufficient to
recommend
Dong Quai: Thought to enhance endogenous estrogens.
1RCT, no better than placebo
TCM: Unconvincing data in Western trials, more success
in trials of Asian women
Acupuncture: Evidence inconclusive
Baber R. Maturitas 2010; 66: 344-49
Hickey M, Baber R Drug Safety 2005;28: 1085-1100
Prescription treatments for
vasomotor symptoms
Clonidine
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25-50ug bd
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Alpha adrenoreceptor agonist,
reduces vasoconstriction
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Clinical effect modest side
effects:
constipation,
dry
mouth, drowsiness
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Long term data lacking
Boekhout A H et al. JCO 2011
Gabapentin for hot flushes
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Gamma
amino
butyric
acid
analogue
used
as
anticonvulsant
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Probably acts as hypothalamic thermoregulatory
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4 RCTs show significant reduction in vasomotor
symptoms at 900mg per day with a clear dose response
relationship
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Initial side effects include drowsiness, confusion and
ataxia
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Start with 300mg and build up slowly as required
Can be used in women already taking SSRI/SNRI
Hickey M, Baber R Drug Safety 2005;28: 1085-1100 Butt et al 2008 Reddy et al 2006, Aguirre et al 2010, Pinkerton et al 2014
Pregabalin for hot flashes
Loprinzi et al JCO 2010
Antidepressants for hot flushes
Name
Reduction in hot flushes
Duration of studies
Desvenlafaxine
100mg
64% (vs 51% placebo)
One year
Improved sleep
Nausea, constipation,
dysfunction
sexual
Venlafaxine 75mg
SR
60% (vs 27% placebo)
8 weeks
Improved sleep
Nausea, constipation,
dysfunction
sexual
Escitalopram (1020mg)
55 % (vs 36% placebo)
8 weeks
Improved sleep, mood, quality
of life and hot flash interference
Does not impair sexual function.
No discontinuation syndr at
10mg
Citalopram 10mg
49% (vs 23% placebo)
6 weeks
9 months
Does not impair sexual function.
No discontinuation syndrome
Ineffective
Fluoxetine 20mg
50% (vs 36% placebo)
6 weeks
9 months
Nausea, constipation, sexual
dysfunction
Ineffective/ AND PAROXETINE?
Paroxetine 12.5mg
56% (vs 28% placebo)
6 weeks
Paroxetine 7.5mg
43% (vs 37% placebo)
12 weeks
Nausea, fatigue, dizzyness,
insomnia. No discontinuation
syndrome at lower doses
No change in sexual function
Improved sleep and reduced
burden of hot flashes
40% (vs 32% placebo)
Additional benefits
24 weeks
Loprinzi et al 2000 and 2002,Stearns et al 2005, Evans et al 2006, Speroff et al 2008, Pinkerton et Al 2013. Simon et al 2013, Freeman et al 2012, Carpenter et
al 2012, Ensrud et al 2012, Joffe et al, in prep, Carpenter et al, 2012, La Croix et al 2012, Reed et al 2012, Suvanto-Luukkonen et al 2005, Pinkerton et al NAMS
Venlafaxine 75mg equivalent to
0.25mg estradiol for VMS
Joffe H et al JAMA Internal Medicine July 2014 Volume 174, Number 7
Considerations for SSRI/SRNI
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Many middle aged women will
already be taking SSRI/SNRI for
depression
Side effects are common
Some products may cause
discontinuation syndromes
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Primarily short-acting agents:
Paroxetine, (des)venlafaxine
Fluoxetine and paroxetine may
interact with tamoxifen
Stearns et al 2004, 2006, Jin et al 2005,
HRT after Breast Cancer
Three major Randomized trials
 HABITS (Hrt After Breast cancer Is iT Safe)
- 345 women, mean age 55, 2.1year follow up
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Stockholm trial
- 378 women, median age 56, 4.1 year follow up
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LIBERATE
- 3098 women, median age 53, 3 year follow up
HRT after Breast Cancer
HABITS: Median follow up 2.1 years
 RR of breast cancer 3.5 (1.5-8.1)
 26% node positive
 21% tamoxifen use
 Most using continuous combined HT
STOCKHOLM: Median follow up 4.1 years
 RR of breast cancer 0.82 (0.35 – 1.9)
 16% node positive
 52% tamoxifen use
 73% Estrogen only or long cycle (3/12) progestin
Holmberg L Lancet 2004;363:453-4, von Schoultz E J Natl Canc Inst 2005;97:533-5
Breast Cancer recurrence (I.T.T)
HR Livial v Placebo (95% CI)
HR = 1.40
95% CI: 1.14-1.70
Kenemans P et al Lancet Oncology 2009;10:135-146
Hormone therapy in women at
high risk of breast cancer
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Family history has no additive impact on breast cancer risk with HRT use1,2
although women with gene mutations are at vastly increased lifetime risk of
breast cancer
HRT use and family history had independent and non interacting risk factors
for breast cancer in WHI3
Long term observational studies have reported no extra risk for those using
HRT with a family history of breast cancer
HRT following risk reduction surgery appears not to increase risk4,5
HRT in such women should use minimal progestrogen and ideally
progesterone or dydrogesterone
1. Rippy L Marsden J Climacteric 2006;9:404-15
2. Sellars T et al Ann Intern Med 1997;127:973-80
3. Gramling R et al Epidemiology 2009;20:752-6
4. Rebeck T et al J Clin Oncol 2005;23:7804-10
5. Eisen J et al J Nat Cancer Inst. 2008;100:1361-67
Cognitive Behavior Therapy
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No change in digital thermography
Reduces troublesomeness of vasomotor symptoms
by >50% in breast cancer patients
Side effects
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Improved mood
Reduced anxiety
Mann et al, 2012, Ayres et al 2012
Managing Menopause in high risk
women
USING THE EVIDENCE TO GUIDE PRACTICE
Clinical Guidance: Managing
Menopause in high risk women
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Provide information about menopause and its management
prior to chemotherapy
Try and work out what is causing the hot flushes – you may need
to use several interventions
For troublesome VMS start with SNRI or Gabapentin
Consider increasing gabapentin at night if sleep disturbance
Most work within a week
Use non-pharmacological methods (CBT/mindfulness) to reduce
impact
Hickey et al 2008, 2012, Finch and Narod 2013, van Oostrom et al 2003, Scott et al, In press, Haines et al NAMS
Managing menopausal symptoms
after breast cancer
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Attention to life style factors
Avoid alternative therapies and practitioners
Liason with Surgeon / Oncologist / GP
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Reduce dose of adjuvant therapy
Vaginal lubricants, moisturisers or Oestriol ( Ospemifene C/I)
Clonidine, SSRI / SNRI, Gabapentin
Stellate Ganglion Block,
Cognitive Behavioural Therapy
Hickey M, Baber R Drug Safety 2005;28: 1085-1100
MacLennan A H Climacteric 2011;14:209-17
Model of multidisciplinary care:
Menopause Symptoms After Cancer Clinic
(MSAC)
Patient referred to MSAC Clinic
Assessment
Treatment plan
Patient seen by menopause
specialist
Information
Patient seen by
nurse specialist
Evidence-based
Clinical guidelines
Management Issues resolved by
Multidisciplinary team
Data collection
Hickey et al 2008, 2010, Marino et al 2013, Marino et al 2014